System and method for evaluating mechanical cardiac dyssynchrony based on multiple impedance vectors using an implantable medical device

ABSTRACT

Techniques are provided for evaluating mechanical dyssynchrony within the heart of patient in which a pacemaker, implantable cardioverter-defibrillator (ICD) or other medical device is implanted. In one example, a set of cardiogenic impedance signals are detected along different sensing vectors passing through the heart of the patient, particularly vectors passing through the ventricular myocardium. A measure of mechanical dyssynchrony is detected based on differences, if any, among the cardiogenic impedance signals detected along the different vectors. In particular, differences in peak magnitude delay times, peak velocity delay times, peak magnitudes, and waveform integrals of the cardiogenic impedance signals are quantified and compared to detect abnormally contracting segments, if any, within the heart of the patient. Warnings are generated upon detection of any significant increase in mechanical dyssynchrony. Diagnostic information is recorded for clinical review. Pacing therapies such as cardiac resynchronization therapy (CRT) can be activated or controlled in response to mechanical dyssynchrony to improve the hemodynamic output of the heart.

FIELD OF THE INVENTION

The invention generally relates to implantable medical devices, such aspacemakers and implantable cardioverter-defibrillators (ICDs), and inparticular to techniques for detecting and evaluating mechanicaldyssynchrony within the heart of a patient using such devices, includingpatients with heart failure.

BACKGROUND OF THE INVENTION

Heart failure is a debilitating disease in which abnormal function ofthe heart leads in the direction of inadequate blood flow to fulfill theneeds of the tissues and organs of the body. Typically, the heart losespropulsive power because the cardiac muscle loses capacity to stretchand contract. Often, the ventricles do not adequately eject or fill withblood between heartbeats and the valves regulating blood flow becomeleaky, allowing regurgitation or back-flow of blood. The impairment ofarterial circulation deprives vital organs of oxygen and nutrients.Fatigue, weakness and the inability to carry out daily tasks may result.Not all heart failure patients suffer debilitating symptoms immediately.Some may live actively for years. Yet, with few exceptions, the diseaseis relentlessly progressive.

As heart failure progresses, it tends to become increasingly difficultto manage. Even the compensatory responses it triggers in the body maythemselves eventually complicate the clinical prognosis. For example,when the heart attempts to compensate for reduced cardiac output, itadds muscle causing the ventricles (particularly the left ventricle) togrow in thickness in an attempt to pump more blood with each heartbeat.This places a still higher demand on the heart's oxygen supply. If theoxygen supply falls short of the growing demand, as it often does,further injury to the heart may result. The additional muscle mass mayalso stiffen the heart walls to hamper rather than assist in providingcardiac output. A particularly severe form of heart failure iscongestive heart failure (CHF) wherein the weak pumping of the heartleads to build-up of fluids in the lungs and other organs and tissues.

Heart failure is often associated with electrical signal conductiondefects within the heart. The natural electrical activation systemthrough the heart involves sequential events starting with thesino-atrial (SA) node, and continuing through the atrial conductionpathways of Bachmann's bundle and internodal tracts at the atrial level,followed by the atrio-ventricular (AV) node, the Bundle of His, theright and left bundle branches, with final distribution to the distalmyocardial terminals via the Purkinje fiber network. Any of theseconduction pathways may potentially be degraded.

A common conduction defect arising in connection with CHF is left bundlebranch block (LBBB). The left bundle branch forms a broad sheet ofconduction fibers along the septal endocardium of the left ventricle andseparates into two or three indistinct fascicles. These extend towardthe left ventricular apex and innervate both papillary muscle groups.The main bundle branches are nourished by septal perforating arteries.In a healthy heart, electrical signals are conducted more or lesssimultaneously through the left and right bundles to trigger synchronouscontraction of both the septal and postero-lateral walls of the leftventricle. LBBB occurs when conduction of electrical signals through theleft bundle branch is delayed or totally blocked, thereby delayingdelivery of the electrical signal to the left ventricle and altering thesequence of activation of that ventricle. The impulse starts in theright ventricle (RV) and crosses the septum causing the interventricularseptum to depolarize and hence, contract, first. The electrical impulsecontinues to be conducted to the postero-lateral wall of the leftventricle causing its activation and depolarization but, due to aninability to use the native conduction system, this activation andcontraction is delayed. As such, the posterolateral wall of the leftventricle (LV) only starts to contract after the interventricular septumhas completed its contraction and is starting to relax. LBBB thusresults in an abnormal activation of the left ventricle inducingdesynchronized ventricular contraction (i.e. ventricular dyssynchrony)and impairment in cardiac hemodynamic performance.

Degeneration of the electrical conduction system as manifested by LBBBor other conduction defects may arise due to an acute myocardialinfarction but is usually associated with degeneration as a result ofchronic ischemia, left ventricular hypertension, general aging andcalcification changes, especially any form of cardiac myopathy thatresults in overt CHF. Present treatments are directed towards correctingthis electrical correlate by pacing on the left side of the heart and/orpacing on both sides of the left ventricle (lateral-posterior wall andseptum) to improve contractile coordination. One particular techniquefor addressing LBBB is cardiac resynchronization therapy (CRT), whichseeks to normalize asynchronous cardiac electrical activation bydelivering synchronized pacing stimulus to both sides of the ventriclesusing pacemakers or ICDs equipped with biventricular pacing capability,i.e. CRT seeks to reduce or eliminate ventricular dyssynchrony.

Ventricular stimulus is synchronized so as to help to improve overallcardiac function. This may have the additional beneficial effect ofreducing the susceptibility to life-threatening tachyarrhythmias. WithCRT, pacing pulses are delivered directly to the left ventricle in anattempt to ensure that the left ventricular myocardium will contractmore uniformly. CRT may also be employed for patients whose nerveconduction pathways are corrupted due to right bundle branch block(RBBB) or due to other problems such as the development of scar tissuewithin the myocardium following a myocardial infarction. CRT and relatedtherapies are discussed in, for example, U.S. Pat. No. 6,643,546 toMathis, et al., entitled “Multi-Electrode Apparatus and Method forTreatment of Congestive Heart Failure”; U.S. Pat. No. 6,628,988 toKramer, et al., entitled “Apparatus and Method for Reversal ofMyocardial Remodeling with Electrical Stimulation”; and U.S. Pat. No.6,512,952 to Stahmann, et al., entitled “Method and Apparatus forMaintaining Synchronized Pacing”.

With conventional CRT, an external Doppler-echocardiography system maybe used to noninvasively assess cardiac function. It can also be used toassess the effectiveness of any programming changes on overall cardiacfunction. Then, biventricular pacing control parameters of the pacemakeror ICD are adjusted by a physician using an external programmer in anattempt to synchronize the ventricles and to optimize patient cardiacfunction. For example, the physician may adjust the interventricularpacing delay, which specifies the time delay between pacing pulsesdelivered to the right and left ventricles, in an attempt to maximizecardiac output. To assess the effectiveness of any programming change,Doppler-echocardiography, external impedance cardiography or some otherindependent measure of cardiac function is utilized. However, thisevaluation and programming requires an office visit and is therefore atimely and expensive process. Moreover, when relying on any externalhemodynamic monitoring system, the control parameters of the pacemakeror ICD cannot be automatically adjusted to respond to on-going changesin patient cardiac function.

Accordingly, it is desirable to configure an implantable device todetect and evaluate the degree of ventricular dyssynchrony within apatient, particularly within those suffering from heart failure, and toautomatically adjust the CRT pacing parameters to reduce the degree ofdyssynchrony and improve cardiac output. Heretofore, various techniquesfor use by implantable devices for evaluating dyssynchrony have usuallyexploited the relative timing of electrical events within anintracardiac electrogram (IEGM) signal sensed by the device to detectelectrical dyssynchrony. Exemplary techniques for detecting ventricularelectrical dyssynchrony based on IEGM signals and for delivering CRT inresponse thereto are set forth in some of the above-cited patents. See,also, U.S. Pat. No. 7,676,264, of Pillai et al., filed on Apr. 13, 2007,entitled “Systems and Methods for use by an Implantable Medical Devicefor Evaluating Ventricular Dyssynchrony based on T-Wave Morphology.”

However, the cardiac synchrony that is restored using IEGM-basedtechniques is principally electrical synchrony. In a diseasedmyocardium, though, electrical synchrony is not synonymous withmechanical synchrony, the latter of which is responsible for improvedhemodynamic output of the heart. Furthermore, left ventricularactivation alone is not a unitary process; it is often the case thatvarious segments or portions of the LV can be asynchronous with respectto each other despite otherwise acceptable electrical performance.

Accordingly, it is desirable to provide techniques for detecting andevaluating ventricular mechanical dyssynchrony for use in controllingCRT or other therapies, and it is to this end that the invention isprimarily directed.

SUMMARY OF THE INVENTION

In an exemplary embodiment, a method is provided for use with animplantable medical device for detecting and evaluating mechanicalcardiac dyssynchrony. Briefly, a set of cardiogenic impedance signalsare detected along different sensing vectors within the patient. Ameasure of mechanical dyssynchrony is detected in the heart of thepatient based on a comparison of the set of cardiogenic impedancesignals. The measure includes information identifying abnormallycontracting segments, if any, within the heart of the patient. Then, atleast one function of the implantable device is controlled based on themeasure of mechanical dyssynchrony. Such device functions can include,e.g., the recording of diagnostic information pertaining to mechanicaldyssynchrony, the generation of warning signals indicating anysubstantial increase in mechanical dyssynchrony, or the activation oradjustment of CRT or other therapies to improve the hemodynamic outputof the heart.

In an illustrative example, the measure of mechanical dyssynchrony isobtained by detecting differences among a set of five cardiogenicimpedance signals sensed within the ventricles of a patient using apacemaker or ICD equipped with multipolar pacing/sensing leads. Anysignificant differences among the five cardiogenic impedance signals aregenerally indicative of ventricular mechanical dyssynchrony within theheart. Exemplary differences that are exploited include differences in:(1) peak magnitude delay times of the cardiogenic impedance signals; (2)peak velocity delay times of the cardiogenic impedance signals; (3) peakmagnitudes of the cardiogenic impedance signals; and (4) integrals ofthe cardiogenic impedance signals. Based on these differences, theimplantable device detects abnormally contracting segments, if any,including any akinetic segments, hypokinetic segments and/or latecontracting segments within the heart of the patient. In addition, thedetected differences are used to generate an overall measure ofmechanical dyssynchrony to assess global hemodynamics of the heart ofthe patient. The use of five impedance sensing vectors provides forgreater resolution for extrapolating hemodynamic performance than asystem exploiting, e.g., only a single impedance sensing vector.

Pacing parameters (such as CRT parameters) are then preferably adjustedso as to decrease the degree of ventricular mechanical dyssynchrony. Byadjusting pacing parameters based on mechanical dyssynchrony derivedfrom cardiogenic impedance signals, the pacing parameters can bepromptly adjusted to respond to changes within the heart, such as torespond to any deterioration in mechanical synchrony arising due to CHF,conduction defects or other ailments such as myocardial infarction oracute cardiac ischemia. Trends in ventricular mechanical dyssynchronywithin the patient may also be identified and tracked to detect, forexample, progression of CHF. Appropriate warnings may be generated forthe patient, the physician, or both.

System and method implementations are described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and further features, advantages and benefits of the inventionwill be apparent upon consideration of the descriptions herein taken inconjunction with the accompanying drawings, in which:

FIG. 1 illustrates pertinent components of an implantable medical systemhaving a pacer/ICD equipped with a mechanical dyssynchrony evaluationsystem;

FIG. 2 provides an overview of the method for evaluating mechanicaldyssynchrony based on cardiogenic impedance signals performed by thesystem of FIG. 1;

FIG. 3 provides an illustrative example of the general technique of FIG.2 wherein certain morphological parameters are derived from thecardiogenic impedance signals for use in evaluating ventricularmechanical dyssynchrony;

FIG. 4 is a graph illustrating an exemplary cardiogenic impedance signalwaveform corresponding to the mechanical contraction of a segment of theheart and, in particular, identifying particular morphological featuresof the impedance waveform that may be exploited by the technique of FIG.3 to evaluate mechanical dyssynchrony;

FIG. 5 provides graphical illustrations of the heart of a patient, alongwith exemplary cardiogenic impedance signal waveforms that may beexploited by the technique of FIG. 3 to detect synchronous anddyssynchronous LV mechanical activation, as well as to identifyhypokinetic, akinetic and late contracting LV segments;

FIG. 6 is a graph illustrating a conduction defect resulting in thesequential mechanical contraction of segments of the heart, which may bedetected using the technique of FIG. 3;

FIG. 7 specifically illustrates peak magnitude delay time processing,which may be performed in accordance with the exemplary technique ofFIG. 3 to detect hypokinetic and late contracting segments;

FIG. 8 specifically illustrates peak velocity delay time processing,which may be performed in accordance with the exemplary technique ofFIG. 3 to detect late contracting segments;

FIG. 9 specifically illustrates peak magnitude processing, which may beperformed in accordance with the exemplary technique of FIG. 3 to detecthypokinetic and akinetic segments;

FIG. 10 specifically illustrates signal integral processing, which maybe performed in accordance with the exemplary technique of FIG. 3 todetect hypokinetic and akinetic segments;

FIG. 11 is a simplified, partly cutaway view, illustrating the pacer/ICDof FIG. 1 along with a more complete set of exemplary leads implanted inthe heart of a patient; and

FIG. 12 is a functional block diagram of the pacer/ICD of FIG. 11,illustrating basic circuit elements that provide cardioversion,defibrillation and/or pacing stimulation in four chambers of the heartand particularly illustrating components for evaluating ventricularmechanical dyssynchrony based on cardiogenic impedance signals and forcontrolling therapy in response thereto.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following description includes the best mode presently contemplatedfor practicing the invention. This description is not to be taken in alimiting sense but is made merely to describe general principles of theinvention. The scope of the invention should be ascertained withreference to the issued claims. In the description of the invention thatfollows, like numerals or reference designators are used to refer tolike parts or elements throughout.

Overview of Implantable Medical System

FIG. 1 illustrates an implantable medical system 8 capable of detectingand evaluating mechanical dyssynchrony within the heart of a patientbased on cardiogenic impedance and also capable of controlling deliveryof appropriate therapy in response thereto. To this end, a pacer/ICD 10(or other implantable medical device) uses one or more multipolarcardiac pacing/sensing leads 12 to detect a set of cardiogenic impedancesignals for comparison to one another. The cardiogenic impedance signalsare detected along different detection vectors representative ofdifferent segments of the heart. In the example of FIG. 1, thecardiogenic impedance signals are detected along a set of sensingvectors 14 between a single RV electrode 16 and a set of separate LVelectrodes 18. This is just one exemplary configuration. A more completeset of leads and electrodes is illustrated in FIG. 11, which isdescribed in detail below.

The pacer/ICD analyzes the cardiogenic impedance signals obtained alongthe different vectors to detect and measure various morphologicalparameters, such as the peak magnitude, peak velocity, waveformintegral, etc. Based on the differences (if any) in the parametersderived from the set of cardiogenic impedance signals, the pacer/ICDdetects and quantifies ventricular mechanical synchrony within thepatient, evaluates its severity, detects abnormally contractingsegments, if any, within the heart of the patient, records diagnosticinformation and issues warnings, if warranted.

For example, if the degree of ventricular mechanical dyssynchrony withinthe patient is found to exceed an acceptable threshold, warning signalsare generated to warn the patient using either an internal warningdevice (which is part of the pacer/ICD) or an external bedside monitor20. The internal warning device may be a vibrating device or a “tickle”voltage device that, in either case, provides perceptible stimulation tothe patient to alert the patient so the patient may then consult aphysician. If a bedside monitor is provided, the bedside monitorprovides audible or visual alarm signals to alert the patient as well astextual or graphic displays. In addition, diagnostic informationpertaining to ventricular mechanical dyssynchrony is transferred to thebedside monitor or is stored within the pacer/ICD for subsequenttransmission to an external programmer (not shown in FIG. 1) for reviewby a physician or other medical professional.

External programmers are typically used only during follow-up sessionswith the patient wherein a clinician downloads information from theimplanted device, reviews the information and then adjusts the controlparameters of the implanted device, if needed, via the programmer.Bedside monitors typically download information more frequently, such asonce per evening, and can be equipped to relay the most pertinentinformation to the patient's physician via a communication network. Inany case, the physician may then prescribe any appropriate therapies toaddress the mechanical dyssynchrony. The physician may also adjust theoperation of the pacer/ICD to activate, deactivate or otherwise controlany therapies that are automatically applied. The bedside monitor may bedirectly networked with a centralized computing system, such as theHouseCall™ system of St. Jude Medical, for immediately notifying thephysician of any significant deterioration in ventricular synchrony.Networking techniques for use with implantable medical systems are setforth, for example, in U.S. Pat. No. 6,249,705 to Snell, entitled“Distributed Network System for Use with Implantable Medical Devices.”

In addition, the pacer/ICD adjusts pacing parameters so as to reduce oreliminate the amount of ventricular mechanical dyssynchrony. That is,the pacer/ICD performs a form of CRT adapted to resynchronize mechanicalcontractions. For example, an AV delay and an LV-RV pacing delay may beadjusted so as to reduce the amount of mechanical dyssynchrony. Fordual-chamber devices, the AV delay specifies the time delay between apaced or sensed atrial event and a paced ventricular event. Forbiventricular pacing devices, the LV-RV delay (sometimes also referredto as just the V-V delay) specifies the time delay between a paced orsensed RV event and a paced LV event. (Note that the LV-RV delay may benegative.)

The pacer/ICD also performs various otherwise conventional operations,such as delivering demand based atrial or ventricular pacing, overdrivepacing therapy, or antitachycardia pacing. The pacer/ICD also monitorsthe heart for atrial or ventricular fibrillation and deliverscardioversion or defibrillation shocks in response thereto.

Hence, FIG. 1 provides an overview of an implantable system capable ofdetecting mechanical cardiac dyssynchrony based on the comparison of aset of cardiogenic impedance signals, and further capable of controllingpacing therapy in response thereto, delivering any appropriatewarning/notification signals, and recording diagnostics. Embodiments maybe implemented that do not necessarily perform all of these functions.For example, embodiments may be implemented that provide only fordetection of mechanical dyssynchrony and generation of warning signalsbut not for automatic control of pacing therapy. Some implementationsmay not employ a bedside monitor. These are just a few exemplaryembodiments. No attempt is made herein to describe all possiblecombinations of components that may be provided in accordance with thegeneral principles of the invention. In addition, note that theparticular locations of the implanted components shown in FIG. 1 aremerely illustrative and may not necessarily correspond to actual implantlocations.

Overview of Ventricular Mechanical Dyssynchrony Evaluation Techniques

FIG. 2 broadly summarizes cardiogenic impedance-based techniques of theinvention that may be performed by the pacer/ICD of FIG. 1 or by anyother suitable device. Briefly, beginning at step 100, the pacer/ICDdetects a set of cardiogenic impedance signals along different sensingvectors within the patient, such as by measuring impedance betweendifferent pairs of electrodes on the multipolar leads. (Detection ofimpedance typically involves generating impedance detection pulses fromwhich a raw impedance signal is derived. The raw impedance signal isthen processed to derive or extract the cardiogenic portion of theimpedance signal, i.e. that portion of the signal affected by thebeating of the heart. This is discussed in more detail below.)

At step 102, the pacer/ICD then detects a measure of mechanicaldyssynchrony in the heart of the patient based on the cardiogenicimpedance signals, including detecting abnormally contracting segments,if any, within the heart of the patient, such as by comparingmorphological features of the cardiogenic impedance signals that areaffected by increasing mechanical dyssynchrony. Illustrative techniquesare described below wherein peak magnitudes, peak time derivatives, andtheir timing intervals are exploited, alone or in combination. At step104, the pacer/ICD then record diagnostics, generate warnings, delivertherapy or control other devices functions based on the measure ofmechanical dyssynchrony or the detection of abnormally contractingsegments. As already explained, the diagnostic data may be transmittedto an external device, such as a bedside monitor or external programmerfor subsequent review by a clinician. Warning signals may be generatedin response to any significant increase in ventricular mechanicaldyssynchrony, which may be indicative of the progression of heartfailure or other cardiovascular diseases. Steps 100-104 may be repeatedin a loop so as to periodically adjust therapy.

Turning now to the remaining figures, various exemplary systems andtechniques for detecting ventricular mechanical dyssynchrony based oncardiogenic impedance signal parameters will now be described in detail.

Illustrative Ventricular Mechanical Dyssynchrony Evaluation Examples

FIGS. 3-5 illustrate exemplary techniques for evaluating ventricularmechanical dyssynchrony to detect hypokinetic segments, akineticsegments, late contracting segments of the heart and to assess globalheart hemodynamics.

Beginning at step 200 of FIG. 3, the pacer/ICD measures raw impedancesignals along each of a set of sensing vectors passing through the heartof the patient and, at step 202, extracts a cardiogenic impedance signalfrom each of the raw impedance signals (where a “cardiogenic impedancesignal” is an signal representative of variations caused by the beatingof the heart in impedance or equivalent electrical parameters.)

That is, the device measures a raw impedance signal along each of theselected sensing vectors by applying impedance detection pulses alongthe vectors, then detecting the resulting impedance signals or values. Aparticularly effective tri-phasic impedance detection pulse for use indetecting impedance is described in pending U.S. patent application Ser.No. 11/558,194 of Panescu et al., filed Nov. 9, 2006, entitled“Closed-Loop Adaptive Adjustment of Pacing Therapy based on CardiogenicImpedance Signals Detected by an Implantable Medical Device.” However,other suitable impedance detection pulses or waveforms may instead beexploited. Once the raw impedance signal is detected, the cardiogenicportion of the signal is extracted by, for example, filtering outvariations in the raw impedance signal due to patient respiration orother factors. The patent application to Panescu et al. discussestechniques for extracting a cardiogenic impedance signal from a rawsignal.

Insofar as the sensing vectors are concerned, each pair of electrodes ofthe pacing/sensing lead system of the implantable medical systemrepresents a different candidate impedance sensing vector. A set ofsensing vectors is selected in advance (via device programming) fromamong the candidate vectors. Sensing vectors are preferably selectedsuch that each includes at least one electrode mounted on or in theventricular myocardium so that the impedance signals detected alongthose vectors are thereby strongly affected by ventricular contractions.That is, electrode pairs are selected such that contraction of theventricular myocardium significantly changes the impedance between theelectrode pairs so as to produce a strong time-varying impedancewaveform representative of ventricular contraction.

In one particular example (described below with reference to FIG. 5), anRV ring electrode is used in combination with each of a set of five LVelectrodes of a multipolar lead so as to defined a set of five sensingvectors: RVring—LVe1; RVring—LVe2; RVring—LVe3; RVring—LVe4, etc.However, other combinations of electrodes can be used to define sensingvectors—so long as the resulting impedance signals are affected by themechanical contraction of the heart to thereby have a cardiogeniccomponent. The use of electrodes mounted on or in the LV of the patientis preferred since the resulting signals will be strongly affected bymechanical contraction of the LV and relatively free of variations dueto respiration or other factors.

Note also that, rather than detecting impedance, other relatedelectrical signals can be exploited, such as admittance, resistance orconductance or their equivalents. Admittance is the numerical reciprocalof impedance. Conductance is the numerical reciprocal of resistance. Ingeneral, impedance and admittance are vector quantities, which may berepresented by complex numbers (having real and imaginary components.)The real component of impedance is resistance. The real component ofadmittance is conductance. When exploiting only the real components ofthese values, conductance can be regarded as the reciprocal ofimpedance. Likewise, when exploiting only the real components,admittance can be regarded as the reciprocal of resistance. Immittancerepresents either impedance or admittance. For the sake of generality,the term “impedance” as used herein encompasses any of these equivalentelectrical signal parameters. These may also be referred to asimmittance-based parameters.

At step 204, the pacer/ICD then compares the cardiogenic impedancesignals detected along the different vectors to identify differences inmorphological parameters affected by mechanical dyssynchrony includingone or more of: (1) peak magnitude delay times of the cardiogenicimpedance signals; (2) peak velocity delay times of the cardiogenicimpedance signals; (3) peak magnitudes of the cardiogenic impedancesignals; and (4) integrals of the cardiogenic impedance signals.

FIG. 4 illustrates these parameters by way of an exemplary impedancesignal or waveform 212 corresponding to the contraction of the heartalong one particular segment of the heart (i.e. along once sensingvector between one pair of electrodes.) In the example, an A-pulse isapplied to the atria at time 214, resulting in the electricaldepolarization of the atria shortly thereafter. Atrial depolarization ismanifest within the RA IEGM as a P-wave 216. The slight delay betweendelivery of the A-pulse and depolarization of the atria is due to thetime required for the atrial myocardial fibers to begin to depolarize inresponse to the stimulus. Following an atrioventricular conduction timedelay, the ventricles then electrically depolarize and contract. Thedepolarization of the ventricles is manifest in the IEGM as aQRS-complex, which is typically much larger than the P-wave. (For thesake of clarity in illustrating other signals of interest, the largeQRS-complex is not shown in the figure.)

Depolarization of the ventricles causes the ventricles to contract,which in turn causes a change in the magnitude of an impedance signalmeasured between a pair of sensing electrodes having a sensing vectorcrossing the ventricles, resulting in time-varying impedance waveform212. The impedance along the sensing vector changes as the myocardiumcontracts primarily because the amount of fluid (i.e. blood) between theelectrodes along the vector decreases as the ventricles contract, thusdecreasing the impedance between the electrodes. In other words,ventricular contraction causes a negative deflection in an impedancesignal relative to a baseline. With the techniques described herein, themagnitude (i.e. the absolute value) of the impedance signal is used sothat the polarity of the impedance signal (negative deflection vs.positive deflection) is not important.

In the particular example of FIG. 4, the magnitude of the impedancesignal increases quickly as the ventricles contract, then decreases moreslowly as the ventricles relax back to their original state. As theventricular myocardium relaxes, the ventricles electrically repolarize.Repolarization of the ventricles is manifest within the IEGM as aT-wave. (For the sake of clarity in illustrating other signals ofinterest, the T-wave is not shown in the figure.)

To detect the peak magnitude delay time 218 of the cardiogenic impedancesignal, the pacer/ICD first detects the peak magnitude 220 of theabsolute value of the impedance waveform (relative to a baseline value222), then determines the time interval from A-pulse delivery time 214to the peak magnitude time 224. To detect the peak velocity delay time,the pacer/ICD determines the first time derivative of the cardiogenicimpedance (CI) signal (i.e. dCI/dt), then detects the maximum value ofthe time derivative. This maximum value represents the maximum speed orvelocity of the ventricular myocardium (along the sensing vector). Inthe example of FIG. 4, the maximum velocity occurs at time 226. Thepacer/ICD then determines the time interval from A-pulse delivery time214 to the peak velocity time 226, which is identified in the figure asdelay interval 228.

For the peak magnitude of the impedance signal, the pacer/ICD merelyuses the peak magnitude value already determined (during detection ofthe peak magnitude time delay.) In FIG. 4, this peak magnitude value isspecifically shown by way of arrow 230. To detect the integral 232 ofthe cardiogenic impedance signal, the pacer/ICD sums or integrates thearea under the impedance waveform using otherwise conventional numericalintegration techniques.

The morphological parameters are detected along each of the selected setof sensing vectors. Hence, if there are five sensing vectors, thepacer/ICD will determined five separate values for each of theparameters, i.e. five separate values for peak magnitude time delay,peak velocity time delay, etc. (Preferably, each of the variousmorphological parameters detected by the pacer/ICD along a givenimpedance sensing vector are ensemble averaged over a set of heartbeatsbefore the morphological parameters are calculated. This will bediscussed further below.)

Returning to FIG. 3, the parameters detected within step 204 for theseparate sensing vectors are compared against one another to detectdifferences, if any. For the example where there are five sensingvectors, the pacer/ICD numerically quantifies the differences betweenthe five separate values for peak magnitude time delay, then separatelyquantifies the differences between the five separate values for peakvelocity time delay, etc. Any of a variety of otherwise conventionalnumerical comparison techniques can be used to quantify the differencesamong these values such as by, e.g., calculating standard deviationvalues. In general, the greater the differences among the values derivedfrom the different sensing vectors, the greater the degree of mechanicaldyssynchrony.

At step 206 of FIG. 3, the pacer/ICD, then detects akinetic segments,hypokinetic segments and late contracting segments based on thedifferences in the morphological parameters of the cardiogenic signal.

FIG. 5 illustrates exemplary hypokinetic segments and late contractingsegments, along with cut-away views of the heart of a patientillustrating five sensing vectors. In particular, the figure illustratesa heart 250 with an RV lead 252 (having at least an RV ring electrode)and an LV lead 254 (also called a coronary sinus lead, see below) with aset of LV electrodes. Five cardiogenic impedance sensing vectors 256 areprovided between the RV ring electrode and the LV electrodes and areidentified herein as CI(E1)-CI(E5).

The figure further illustrates mechanically synchronous LV activation byway of heart illustration 250′ and mechanically dyssynchronous LVactivation by way of heart illustration 250″. In this example, duringsynchronous activation, the electrodes of lead 254 are substantiallyuniformly displaced during contraction to a contracted position 258. Assuch, each of the impedance waveforms measured along the differentsensing vectors changes at about the same time and by about the sameamount. This is illustrated by way of impedance waveform graphs 260,each exhibiting similar time delays, magnitudes and waveform shapes. Assuch, each likewise has similar values for peak magnitude delay time,peak velocity delay time, peak magnitude, and waveform integral.

However, during dyssynchronous activation, the electrodes of lead 254are not uniformly displaced during contraction, yielding a non-uniformcontracted position 262. As such, each of the impedance waveformsmeasured along the different sensing vectors changes at somewhatdifferent times and by somewhat different amounts. This is illustratedby way of impedance waveform graphs 264, which no longer exhibit thesame time delays, magnitudes and waveform shapes for each vector. Inthis particular example, the portion or segment of the ventricularmyocardium through which sensing vector CI(E2) passes contracts afterthe other segments have contracted, i.e. it is a late contractingsegment. As a result, the impedance waveform sensed along thecorresponding vector is delayed relative to the other impedancewaveforms, as shown by way of waveform 266. Accordingly, the latecontracting segment will have a different value for the peak magnitudedelay time and the peak velocity delay time as compared to the otherimpedance signals. In the example, that particular segment of themyocardium also contracts by a smaller amount (i.e. it is hypokinetic),resulting in a smaller waveform, as also shown by way of waveform 266.Accordingly, the impedance waveform sensed along the correspondingvector has a smaller peak magnitude and a smaller integral value.

Although not shown in the example of FIG. 5, in some patients, somesegments of the ventricular myocardium might not contract at all,resulting in little or no change in impedance along the correspondingsensing vector, i.e. the segment is akinetic. Accordingly, the impedancewaveform sensed along that vector will be substantially flat. The peakmagnitude (measured relative to baseline) and the signal integral willtherefore both be near zero.

Hence, FIG. 5 illustrates an example wherein healthy synchronouscontraction of the LV myocardium results in impedance waveforms havingsubstantially similar time delays (relative to the A-pulse) and alsohaving substantially similar peak magnitudes and signal integral values.As can be appreciated, even within a healthy heart, there is typicallysome variation in these values from vector to vector. Accordingly, onlysignificant deviations among these values are deemed to be indicative ofmechanical dyssynchrony. Also, with regard to peak magnitude values andsignal integral values, even within a healthy heart there can bevariations in these values from one sensing vector to another due to therelative orientations of the sensing vectors. In particular, a sensingvector utilizing an LV electrode near the apex of the ventricles mightexhibit a smaller deflection in the impedance signal during contractionthan a sensing vector utilizing an LV electrode further from the apex ofthe ventricles. In the example of FIG. 5, sensing vector 270 may exhibitless of a change in impedance during contraction than sensing vector272, even though the LV is contracting synchronously. Hence, themeasured values of peak magnitude and signal integral are preferablynormalized. For example, following device implant, nominal values forpeak magnitude and waveform signal integral along each sensing vectorare measured, then normalized. Thereafter, only variations from thosenormalized values are used to detect hypokinetic segments.

Normalization is not required for the aforementioned time delay values.Within a healthy heart, these time delay values (measured relative tothe time of delivery of the A-pulse) are substantially similar from onevector to another even though the various LV electrodes of the differentvectors are positioned at different locations and at different distancesfrom the atria. That is, within a healthy heart, all segments of theventricular myocardium contract at substantially the same timeregardless of their relative location within the LV. Note, though, thatthe actual duration of the interval from A-pulse to LV contraction willdepend on patient heart rate and other factors. Accordingly, a uniformincrease or decrease in the time delay values measured along all of thevectors is not indicative of mechanical dyssynchrony. Rather, it is thevariation (if any) in time delay values from one vector to another thatis instead indicative of dyssynchrony.

Note also that, within some unhealthy hearts, conduction defects cancause segments of the LV to contract sequentially, rather thansimultaneously. This is illustrated by way of the graphs of FIG. 6. Thatis, within FIG. 6, a set of cardiogenic impedance waveforms 274 areillustrated wherein there is a sequentially variation in contractiontimes, indicative of possible conduction defects within the heart of thepatient. This is yet another form of dyssynchrony that the pacer/ICD candetect using the techniques of the invention.

Returning to FIG. 3, at step 208, the pacer/ICD then generates a measureof global mechanical synchrony of the heart of the patient based on thedifferences (if any) in the cardiogenic signals. For example, usingotherwise standard numerical techniques, the pacer/ICD can generate orcalculate a single numerical value (e.g. a metric) indicative of thetotal amount of variation among the various morphological parameters ofthe cardiogenic impedance signal. At step 210, the pacer/ICD assessesthe global hemodynamics of the heart of the patient based on the measureof global mechanical synchrony. The greater the value of the metric, thegreater the amount of mechanical dyssynchrony, i.e. the poorer theoverall state of global hemodynamics. For example, the metric may becompared against one or more threshold values indicative of globalhemodynamics. The metric may be tracked over time to detect trendsindicative of progression of heart failure. Warning signals can then begenerated, therapy controlled, etc., as already explained. Diagnostictrend data can be stored.

The assessment of the hemodynamics of the heart can be performed inconjunction with other evaluation systems and techniques that alsoexploit impedance data, IEGM signals or other parameters detected withinthe patient. See, for example, techniques described in theaforementioned U.S. Pat. No. 7,676,264 of Pillai et al., as well aspending U.S. patent application Ser. No. 11/558,194, of Panescu et al.,filed Nov. 9, 2006, entitled “Closed-Loop Adaptive Adjustment of PacingTherapy based on Cardiogenic Impedance Signals Detected by anImplantable Medical Device”; pending U.S. patent application Ser. No.11/557,887, of Shelchuk, filed Nov. 8, 2006, entitled “Systems andMethods for Evaluating Ventricular Dyssynchrony Using Atrial andVentricular Pressure Measurements obtained by an Implantable MedicalDevice”; and U.S. Pat. No. 7,072,715 to Bradley, entitled “ImplantableCardiac Stimulation Device for and Method of Monitoring Progression orRegression of Heart Disease by Monitoring Evoked Response Features.”

As noted, ventricular dyssynchrony may arise due to heart failure andhence any degradation in ventricular dyssynchrony might be indicative ofprogression of heart failure. Depending upon the capabilities of thepacer/ICD, heart failure may be corroborated by other suitable detectiontechniques. See, for example, U.S. Pat. No. 6,922,587, entitled “Systemand Method for Tracking Progression of Left Ventricular DysfunctionUsing Implantable Cardiac Stimulation Device”; U.S. Pat. No. 6,942,622,entitled “Method For Monitoring Autonomic Tone”; U.S. Pat. No.6,748,261, cited above, U.S. Pat. No. 6,741,885, entitled “ImplantableCardiac Device For Managing the Progression of Heart Disease andMethod”; U.S. Pat. No. 6,643,548, entitled “Implantable CardiacStimulation Device for Monitoring Heart Sounds to Detect Progression andRegression of Heart Disease And Method Thereof”; U.S. Pat. No.6,572,557, entitled “System And Method For Monitoring Progression OfCardiac Disease State Using Physiologic Sensors”; U.S. Pat. No.6,527,729, entitled “Method For Monitoring Patient Using AcousticSensor”; U.S. Pat. No. 6,512,953, entitled “System and Method forAutomatically Verifying Capture During Multi-Chamber Stimulation” andU.S. Pat. No. 6,480,733, entitled “Method for Monitoring Heart Failure”,each assigned to Pacesetter, Inc.

See, also, U.S. Pat. No. 7,272,443, filed Dec. 15, 2004, of Bornzin etal., entitled “System and Method for Predicting a Heart Condition Basedon Impedance Values Using an Implantable Medical Device”, and U.S. Pat.No. 7,094,207, filed Mar. 2, 2004, entitled “System and Method forDiagnosing and Tracking Congestive Heart Failure Based on thePeriodicity of Cheyne-Stokes Respiration Using an Implantable MedicalDevice”; and U.S. Pat. No. 7,672,716 of Koh, entitled “QT-Based Systemand Method for Detecting and Distinguishing Dilated Cardiomyopathy andHeart Failure Using an Implantable Medical Device”, also assigned toPacesetter, Inc.

Turning now to FIGS. 7-9, further details regarding the processing ofthe aforementioned morphological parameters will now be provided.

FIG. 7 particularly illustrates peak magnitude delay time processing.Beginning at step 300, A-pulses (or other pacing pulses, such asRV-pulses) are delivered to the heart of the patient so as to provide apoint of origin from which ventricular contraction delays can bemeasured. If the patient is already subject to therapeutic atrial pacing(e.g. to mitigate bradycardia), the pacer/ICD simply delivers A-pulsesin accordance with that on-going therapy. If A-pulses are not alreadybeing delivered, the pacer/ICD can initiate a regime of atrial pacingspecifically for the purposes of evaluating the mechanical synchrony ofthe heart. This may be performed periodically such, e.g., once per day.In any case, at step 302, the pacer/ICD senses and records separatecardiogenic impedance signals along each of N sensing vectors, such asthe five vectors shown in FIG. 5. A greater number of sensing vectorsprovides for greater resolution. Preferably, the pacer/ICD senses andrecords impedance signal waveforms for each of a set of consecutiveheartbeats (such as ten consecutive heartbeats), then ensemble averagesthe waveforms over the set of heartbeats to provide an averaged waveformfor analysis.

At step 304, for each of the N cardiogenic impedance signals, thepacer/ICD then: examines the signal to detect the maximum magnitude inthe signal following the atrial pacing pulse (or other pacing pulse usedas a point of origin) and measures the time delay from the pulse to themaximum point in the absolute value of the signal. This time delay isrecorded as the peak magnitude delay time. At step 306, the pacer/ICDthen compares the peak magnitude delay times derived from each of the Ncardiogenic impedance signals to generate a measure of mechanicaldyssynchrony, where significant differences in peak magnitude delaytimes are representative of significant mechanical dyssynchronies withinthe heart.

At step 308, the pacer/ICD then identifies late contracting segments (ifany) within the heart of the patient by identifying particularcardiogenic impedance signals from the set of N signals where the peakmagnitude delay time is significantly longer than the peak magnitudedelay times of the other cardiogenic impedance signals (as with waveform266 of FIG. 5.) In this regard, the pacer/ICD may exploit apredetermined peak magnitude delay time threshold indicative of anabnormally long time delay. The threshold may be programmed in advanceby the clinician or set to a default value. In one particular example,if the peak magnitude time delay for one particular vector is at least10% longer than the time delays values of the other vectors, the timedelay is deemed to be abnormally long, i.e. the segment is latecontracting. Otherwise routine experimentation can be performed toidentify optimal or preferred threshold values.

Diagnostic information identifying any late contracting segments may berecorded for clinician review. Also, as already explained, the amount ofvariation in the peak magnitude delay times can be incorporated into ametric representative of the global hemodynamics.

FIG. 8 illustrates peak velocity delay time processing. Many of thesteps are the same or similar to those of FIG. 7 and those steps willonly be briefly mentioned. At step 400, A-pulses (or other pacingpulses) are delivered and, at step 402, separate cardiogenic impedancesignals are sensed and recorded for each of N sensing vectors. At step404, for each of the N cardiogenic impedance signals, the pacer/ICDthen: calculates the first time derivative of the signal; detects themaximum magnitude in the signal following the atrial pacing pulse (orother pacing pulse used as a point of origin); and measures the timedelay from the pulse to the maximum point in the time derivative signal.This time delay is recorded as the peak velocity delay time.

At step 406, the pacer/ICD then compares the peak velocity delay timesderived from each of the N cardiogenic impedance signals to generate ameasure of mechanical dyssynchrony. At step 408, the pacer/ICD thenidentifies late contracting segments (if any) within the heart of thepatient relative to a predetermined delay threshold. Diagnosticinformation identifying any late contracting segments is recorded forclinician review. Also, as already explained, the amount of variation inthe peak velocity delay times can be incorporated into the metricrepresentative of the global hemodynamics.

FIG. 9 illustrates peak magnitude processing. At step 500, A-pulses (orother pacing pulses) are delivered and, at step 502, cardiogenicimpedance signals are sensed and recorded. At step 504, for each of Ncardiogenic impedance signals, the pacer/ICD detects and measures themaximum or peak magnitude in the absolute value of signal following theatrial pacing pulse (or other pacing pulse used as a point of origin).At step 506, the pacer/ICD compares normalized versions of the peakmagnitude values derived from the N cardiogenic impedance signals togenerate a measure of mechanical dyssynchrony, where significantdifferences in the normalized peak magnitudes are representative ofsignificant mechanical dyssynchronies within the heart.

At step 508, the pacer/ICD then identifies hypokinetic segments (if any)within the heart of the patient by identifying particular cardiogenicimpedance signals where normalized peak magnitudes are significantlylower than the peak magnitude values of the other cardiogenic impedancesignals (as with waveform 268 of FIG. 5.) The pacer/ICD may exploit apredetermined peak magnitude threshold indicative of an abnormally lowpeak magnitude. The threshold may be programmed in advance by theclinician or set to a default value. In one particular example, if thenormalized peak magnitude for one particular vector is at least 10%lower than the normalized peak magnitudes of the other vectors, thesegment is deemed to be hypokinetic. Otherwise routine experimentationcan be performed to identify optimal or preferred threshold values.

At step 510, the pacer/ICD also identifies akinetic segments (if any)within the heart of the patient by identifying particular cardiogenicimpedance signals where the peak magnitudes are below a minimumacceptable predetermined magnitude threshold. The threshold may beprogrammed in advance by the clinician or set to a default value. In oneparticular example, if the normalized peak magnitude for one particularvector is no greater than 5% of its initial normalized peak magnitude,the segment is deemed to be akinetic. Again, otherwise routineexperimentation can be performed to identify optimal or preferredthreshold values.

FIG. 10 illustrates signal integral processing. At step 600, A-pulses(or other pacing pulses) are delivered and, at step 602, cardiogenicimpedance signals are sensed and recorded. At step 604, for each of Ncardiogenic impedance signals, the pacer/ICD sums or integrates thewaveform of the impedance signal following the atrial pacing pulse (orother pacing pulse used as a point of origin) to produce a signal orwaveform integral. At step 606, the pacer/ICD then compares normalizedversions of the signal integral values derived from the N cardiogenicimpedance signals to generate a measure of mechanical dyssynchrony,where significant differences in the normalized signal integral arerepresentative of significant mechanical dyssynchronies.

At step 608, the pacer/ICD then identifies hypokinetic segments (if any)within the heart of the patient by identifying particular cardiogenicimpedance signals where normalized signal integral are significantlylower than the signal integral values of the other cardiogenic impedancesignals. The pacer/ICD may exploit a predetermined signal integralthreshold indicative of an abnormally signal integral. The threshold maybe programmed in advance by the clinician or set to a default value. Inone particular example, if the normalized signal integral for oneparticular vector is at least 10% lower than the normalized signalintegral of the other vectors, the segment is deemed to be hypokinetic.Again, otherwise routine experimentation can be performed to identifyoptimal or preferred threshold values.

At step 610, the pacer/ICD also identifies akinetic segments (if any)within the heart of the patient by identifying particular cardiogenicimpedance signals where the signal integral are below a minimumacceptable predetermined signal integral threshold. The threshold may beprogrammed in advance by the clinician or set to a default value. In oneparticular example, if the normalized signal integral for one particularvector is no greater than 5% of its initial normalized signal integralvalue, the segment is deemed to be akinetic. Again, otherwise routineexperimentation can be performed to identify optimal or preferredthreshold values.

What have been described are various techniques for evaluating cardiacmechanical dyssynchrony based on impedance parameters and forcontrolling therapy and other functions in response thereto. Althoughdescribed primarily with reference to LV mechanical dyssynchrony, thetechniques of the invention may also be applied, where appropriate, todetecting other forms of mechanical dyssynchrony, such as RV mechanicaldyssynchrony, or even atrial mechanical dyssynchrony. Also, althoughparticular morphological parameters are described herein (peakmagnitude, etc.), these are merely exemplary and other suitableparameters derived from the cardiogenic impedance signals may be used,either additionally or alternatively.

For the sake of completeness, a detailed description of an exemplarypacer/ICD for evaluating cardiac mechanical dyssynchrony will now beprovided. However, principles of invention may be implemented withinother pacer/ICD implementations or within other implantable devices,including stand-alone mechanical dyssynchrony monitoring devices that donot provide pacing/sensing. Furthermore, although examples describedherein involve processing of the various signals by the implanted deviceitself, some operations may be performed using an external device. Forexample, recorded impedance data may be transmitted to an externaldevice, which processes the data to evaluate cardiac mechanicaldyssynchrony. Processing by the implanted device itself is preferred asthat allows prompt changes to pacing control parameters so as to addressany progression in ventricular mechanical dyssynchrony.

Exemplary Pacemaker/ICD

FIG. 11 provides a simplified block diagram of the pacer/ICD, which is amulti-chamber stimulation device capable of treating both fast and slowarrhythmias with stimulation therapy, including cardioversion,defibrillation, and pacing stimulation, as well as being capable ofperforming the impedance-based functions discussed above. To provideatrial chamber pacing stimulation and sensing, pacer/ICD 10 is shown inelectrical communication with a heart 712 by way of a left atrial lead720 having an atrial tip electrode 722 and an atrial ring electrode 723implanted in the atrial appendage. Pacer/ICD 10 is also in electricalcommunication with the heart by way of a right ventricular lead 730having, in this embodiment, a ventricular tip electrode 732, a rightventricular ring electrode 734, a right ventricular (RV) coil electrode736, and a superior vena cava (SVC) coil electrode 738. Typically, theright ventricular lead 718 is transvenously inserted into the heart toplace the RV coil electrode 736 in the right ventricular apex, and theSVC coil electrode 738 in the superior vena cava. Accordingly, the rightventricular lead is capable of receiving cardiac signals, and deliveringstimulation in the form of pacing and shock therapy to the rightventricle.

To sense left atrial and ventricular cardiac signals and to provide leftchamber pacing therapy, pacer/ICD 10 is coupled to a CS lead 724designed for placement in the “CS region” via the CS os for positioninga distal electrode adjacent to the left ventricle and/or additionalelectrode(s) adjacent to the left atrium. As used herein, the phrase “CSregion” refers to the venous vasculature of the left ventricle,including any portion of the CS, great cardiac vein, left marginal vein,left posterior ventricular vein, middle cardiac vein, and/or smallcardiac vein or any other cardiac vein accessible by the CS.Accordingly, an exemplary CS lead 724 is designed to receive atrial andventricular cardiac signals and to deliver left ventricular pacingtherapy using at least a set of left ventricular ring electrodes 725₁-725 ₅, a left ventricular tip electrode 726, and to deliver leftatrial pacing therapy using at least a left atrial ring electrode 727,and shocking therapy using at least a left atrial coil electrode 728.With this configuration, biventricular pacing can be performed. Althoughonly three leads are shown in FIG. 12, it should also be understood thatadditional stimulation leads (with one or more pacing, sensing and/orshocking electrodes) might be used in order to efficiently andeffectively provide pacing stimulation to the left side of the heart oratrial cardioversion and/or defibrillation. Also, it should beunderstood that multiple ring electrodes may additionally oralternatively be provided on the RV lead or on the RA lead. Still moreelectrodes may be provide along the CS lead on or in the left atrium. Inany case, a set of N sensing vectors is therapy provided for use insensing separate cardiogenic impedance signals.

A simplified block diagram of internal components of pacer/ICD 10 isshown in FIG.12. While a particular pacer/ICD is shown, this is forillustration purposes only, and one of skill in the art could readilyduplicate, eliminate or disable the appropriate circuitry in any desiredcombination to provide a device capable of treating the appropriatechamber(s) with cardioversion, defibrillation and pacing stimulation.The housing 740 for pacer/ICD 10, shown schematically in FIG. 12, isoften referred to as the “can”, “case” or “case electrode” and may beprogrammably selected to act as the return electrode for all “unipolar”modes. The housing 740 may further be used as a return electrode aloneor in combination with one or more of the coil electrodes, 728, 736 and738, for shocking purposes. The housing 740 further includes a connector(not shown) having a plurality of terminals, 725 ₁-725 ₅, 742, 743, 744,745 746, 748, 752, 754, 756 and 758 (shown schematically and, forconvenience, the names of the electrodes to which they are connected areshown next to the terminals). As such, to achieve right atrial sensingand pacing, the connector includes at least a right atrial tip terminal(A_(R) TIP) 742 adapted for connection to the atrial tip electrode 722and a right atrial ring (A_(R) RING) electrode 743 adapted forconnection to right atrial ring electrode 723. To achieve left chambersensing, pacing and shocking, the connector includes at least a leftventricular tip terminal (V_(L) TIP) 744, a left atrial ring terminal(A_(L) RING) 746, and a left atrial shocking terminal (A_(L) COIL) 748,which are adapted for connection to the left ventricular tip electrode726, the left atrial ring electrode 727, and the left atrial coilelectrode 728, respectively. To support right chamber sensing, pacingand shocking, the connector further includes a right ventricular tipterminal (V_(R) TIP) 752, a right ventricular ring terminal (V_(R) RING)754, a right ventricular shocking terminal (V_(R) COIL) 756, and an SVCshocking terminal (SVC COIL) 758, which are adapted for connection tothe right ventricular tip electrode 732, right ventricular ringelectrode 734, the V_(R) coil electrode 736, and the SVC coil electrode738, respectively.

At the core of pacer/ICD 10 is microcontroller 760, which controls thevarious modes of stimulation therapy. As is well known in the art, themicrocontroller 760 (also referred to herein as a control unit)typically includes a microprocessor, or equivalent control circuitry,designed specifically for controlling the delivery of stimulationtherapy and may further include RAM or ROM memory, logic and timingcircuitry, state machine circuitry, and I/O circuitry. Typically, themicrocontroller 760 includes the ability to process or monitor inputsignals (data) as controlled by a program code stored in a designatedblock of memory. The details of the design and operation of themicrocontroller 760 are not critical to the invention. Rather, anysuitable microcontroller 760 may be used that carries out the functionsdescribed herein.

The use of microprocessor-based control circuits for performing timingand data analysis functions are well known in the art.

As shown in FIG. 12, an atrial pulse generator 770 and a ventricularpulse generator 772 generate pacing stimulation pulses for delivery bythe right atrial lead 720, the right ventricular lead 730, and/or the CSlead 724 via an electrode configuration switch 774. It is understoodthat in order to provide stimulation therapy in each of the fourchambers of the heart, the atrial and ventricular pulse generators, 770and 772, may include dedicated, independent pulse generators,multiplexed pulse generators or shared pulse generators. The pulsegenerators, 770 and 772, are controlled by the microcontroller 760 viaappropriate control signals, 776 and 778, respectively, to trigger orinhibit the stimulation pulses.

The microcontroller 760 further includes timing control circuitry 779used to control the timing of such stimulation pulses (e.g., pacingrate, atrioventricular delay, atrial interconduction (inter-atrial)delay, or ventricular interconduction (V-V) delay, etc.) as well as tokeep track of the timing of refractory periods, blanking intervals,noise detection windows, evoked response windows, alert intervals,marker channel timing, etc., which is well known in the art. Switch 774includes a plurality of switches for connecting the desired electrodesto the appropriate I/O circuits, thereby providing complete electrodeprogrammability. Accordingly, the switch 774, in response to a controlsignal 780 from the microcontroller 760, determines the polarity of thestimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) byselectively closing the appropriate combination of switches (not shown)as is known in the art.

Atrial sensing circuits 782 and ventricular sensing circuits 784 mayalso be selectively coupled to the right atrial lead 720, CS lead 724,and the right ventricular lead 730, through the switch 774 for detectingthe presence of cardiac activity in each of the four chambers of theheart. Accordingly, the atrial and ventricular sensing circuits, 782 and784, may include dedicated sense amplifiers, multiplexed amplifiers orshared amplifiers. The switch 774 determines the “sensing polarity” ofthe cardiac signal by selectively closing the appropriate switches, asis also known in the art. In this way, the clinician may program thesensing polarity independent of the stimulation polarity. Each sensingcircuit, 782 and 784, preferably employs one or more low power,precision amplifiers with programmable gain and/or automatic gaincontrol and/or automatic sensitivity control, bandpass filtering, and athreshold detection circuit, as known in the art, to selectively sensethe cardiac signal of interest. The automatic gain control and/orautomatic sensitivity control enables pacer/ICD 10 to deal effectivelywith the difficult problem of sensing the low amplitude signalcharacteristics of atrial or ventricular fibrillation. The outputs ofthe atrial and ventricular sense amplifiers may be in the form ofinterrupts. The microcontroller 760 triggers or inhibits the atrial andventricular pulse generators, 770 and 772, respectively, in a demandfashion in response to the absence or presence of cardiac activity inthe appropriate chambers of the heart, as represented by the atrial andventricular event interrupts.

For arrhythmia detection, pacer/ICD 10 utilizes the atrial andventricular sensing circuits, 782 and 784, to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. As used in thissection “sensing” is reserved for the noting of an electrical signal,and “detection” is the processing of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g., AS, VS, and depolarization signals associated with fibrillationwhich are sometimes referred to as “F-waves” or “Fib-waves”) are thenclassified by the microcontroller 760 by comparing them to a predefinedrate zone limit (i.e., bradycardia, normal, atrial tachycardia, atrialfibrillation, low rate ventricular tachycardia, high rate ventriculartachycardia, and fibrillation rate zones) and various othercharacteristics (e.g., sudden onset, stability, physiologic sensors, andmorphology, etc.) in order to determine the type of remedial therapythat is needed (e.g., bradycardia pacing, antitachycardia pacing,cardioversion shocks or defibrillation shocks).

Cardiac signals are also applied to the inputs of an analog-to-digital(A/D) data acquisition system 790. The data acquisition system 790 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device802. The data acquisition system 790 is coupled to the right atrial lead720, the CS lead 724, and the right ventricular lead 718 through theswitch 774 to sample cardiac signals across any pair of desiredelectrodes. The microcontroller 760 is further coupled to a memory 794by a suitable data/address bus 796, wherein the programmable operatingparameters used by the microcontroller 760 are stored and modified, asrequired, in order to customize the operation of pacer/ICD 10 to suitthe needs of a particular patient. Such operating parameters define, forexample, pacing pulse amplitude or magnitude, pulse duration, electrodepolarity, rate, sensitivity, automatic features, arrhythmia detectioncriteria, and the amplitude, waveshape and vector of each shocking pulseto be delivered to the patient's heart within each respective tier oftherapy. Other pacing parameters include base rate, rest rate andcircadian base rate.

Advantageously, the operating parameters of the implantable pacer/ICD 10may be non-invasively programmed into the memory 794 through a telemetrycircuit 800 in telemetric communication with the external device 802,such as a programmer, transtelephonic transceiver or a diagnostic systemanalyzer. The telemetry circuit 800 is activated by the microcontrollerby a control signal 806. The telemetry circuit 800 advantageously allowsintracardiac electrograms and status information relating to theoperation of pacer/ICD 10 (as contained in the microcontroller 760 ormemory 794) to be sent to the external device 802 through an establishedcommunication link 804. Pacer/ICD 10 further includes an accelerometeror other physiologic sensor 808, commonly referred to as a“rate-responsive” sensor because it is typically used to adjust pacingstimulation rate according to the exercise state of the patient.However, the physiological sensor 808 may further be used to detectchanges in cardiac output, changes in the physiological condition of theheart, or diurnal changes in activity (e.g., detecting sleep and wakestates) and to detect arousal from sleep. Accordingly, themicrocontroller 760 responds by adjusting the various pacing parameters(such as rate, AV delay, V-V delay, etc.) at which the atrial andventricular pulse generators, 770 and 772, generate stimulation pulses.While shown as being included within pacer/ICD 10, it is to beunderstood that the physiologic sensor 808 may also be external topacer/ICD 10, yet still be implanted within or carried by the patient. Acommon type of rate responsive sensor is an activity sensorincorporating an accelerometer or a piezoelectric crystal, which ismounted within the housing 740 of pacer/ICD 10. Other types ofphysiologic sensors are also known, for example, sensors that sense theoxygen content of blood, respiration rate and/or minute ventilation, pHof blood, ventricular gradient, etc.

The pacer/ICD additionally includes a battery 810, which providesoperating power to all of the circuits shown in FIG. 12. The battery 810may vary depending on the capabilities of pacer/ICD 10. If the systemonly provides low-voltage therapy, a lithium iodine or lithium copperfluoride cell may be utilized. For pacer/ICD 10, which employs shockingtherapy, the battery 810 must be capable of operating at low currentdrains for long periods, and then be capable of providing high-currentpulses (for capacitor charging) when the patient requires a shock pulse.The battery 810 should also have a predictable discharge characteristicso that elective replacement time can be detected. Accordingly,pacer/ICD 10 is preferably capable of high-voltage therapy andappropriate batteries.

As further shown in FIG. 12, pacer/ICD 10 is shown as having an N-vectorimpedance measuring circuit 812 which is enabled by the microcontroller760 via a control signal 814. The impedance circuit is used to detectseparate cardiogenic impedance signals along vectors between the RV ringelectrode and the five LV ring electrodes, or between other pairs orcombinations of electrodes. Impedance values may also be used fortracking respiration; for surveillance during the acute and chronicphases for proper lead positioning or dislodgement; for measuringrespiration or minute ventilation; for measuring thoracic impedance foruse in setting shock thresholds; for detecting when the device has beenimplanted; and for detecting the opening of heart valves, etc. Theimpedance measuring circuit 817 is advantageously coupled to the switch74 so that any desired combination of electrodes may be used.

In the case where pacer/ICD 10 is intended to operate as an ICD, itdetects the occurrence of an arrhythmia, and automatically applies anappropriate electrical shock therapy to the heart aimed at terminatingthe detected arrhythmia. To this end, the microcontroller 760 furthercontrols a shocking circuit 816 by way of a control signal 818. Theshocking circuit 816 generates shocking pulses of low (up to 0.5joules), moderate (0.5-10 joules) or high energy (11 to 40 joules ormore), as controlled by the microcontroller 760. Such shocking pulsesare applied to the heart of the patient through at least two shockingelectrodes, and as shown in this embodiment, selected from the leftatrial coil electrode 728, the RV coil electrode 736, and/or the SVCcoil electrode 738. The housing 740 may act as an active electrode incombination with the RV electrode 736, or as part of a split electricalvector using the SVC coil electrode 738 or the left atrial coilelectrode 728 (i.e., using the RV electrode as a common electrode).Cardioversion shocks are generally considered to be of low to moderateenergy level (so as to minimize pain felt by the patient), and/orsynchronized with a VF event and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range of 8-40joules), delivered asynchronously (since VF events may be toodisorganized), and pertaining exclusively to the treatment offibrillation. Accordingly, the microcontroller 760 is capable ofcontrolling the synchronous or asynchronous delivery of the shockingpulses.

Microcontroller 760 also includes various components for controlling orperforming the various operations described above with reference toFIGS. 1-10. In particular, the microcontroller includes a multiplecardiogenic impedance signal detector 801 operative to detect aplurality of cardiogenic impedance signals along different sensingvectors within the patient, and a mechanical dyssynchrony evaluationsystem 803 operative to detect a measure of mechanical dyssynchrony inthe heart of the patient based on the cardiogenic impedance signals,including detecting abnormally contracting segments, if any, within theheart of the patient. A mechanical dyssynchrony-based CRT controller 805is operative to control CRT based, at least in part, in the measure ofmechanical dyssynchrony to improve cardiac function. The microcontrolleralso includes a mechanical dyssynchrony-based warning and diagnosticcontroller 807 operative to control the generation of warning signalsand to control recording of diagnostic information within memory 794pertinent to mechanical dyssynchrony. Warnings may be issued viainternal implanted alarm 809 or via bedside monitor 20.

Depending upon the implementation, the various components of themicrocontroller may be implemented as separate software modules or themodules may be combined to permit a single module to perform multiplefunctions. In addition, although shown as being components of themicrocontroller, some or all of these components may be implementedseparately from the microcontroller, using application specificintegrated circuits (ASICs) or the like.

When used in conjunction with an external system such as a bedsidemonitor, the external system can perform some of the mechanicaldyssynchrony evaluation functions, such as by analyzing impedance datatransmitted from the pacer/ICD. This is shown by way of externalmechanical dyssynchrony evaluation system 811 of the bedside monitor. Inother words, not all of the functions need be performed by the pacer/ICDbut functions can be distributed among various systems, some implantedwithin the patient, others external.

While the invention has been described with reference to particularexemplary embodiments, modifications can be made thereto withoutdeparting from scope of the invention. Note also that the term“including” as used herein is intended to be inclusive, i.e. “includingbut not limited to.”

1. A method for use with an implantable medical device for implantwithin a patient, the method comprising: detecting a plurality ofcardiogenic impedance signals along different sensing vectors within thepatient; detecting a measure of mechanical dyssynchrony in the heart ofthe patient based on a comparison of the cardiogenic impedance signals,including detecting abnormally contracting segments, if any, within theheart of the patient; and controlling at least one device function basedon the measure of mechanical dyssynchrony; wherein detecting the measureof mechanical dyssynchrony includes delivering a pacing pulse to theheart of the patient; for each of the cardiogenic impedance signals,examining the signal to detect a maximum in a first time derivative ofthe signal after pulse delivery and then measuring the time delay fromthe pulse to the maximum in the first time derivative; and comparing thepeak velocity delay times derived from the cardiogenic impedance signalsto generate the measure of mechanical dyssynchrony.
 2. The method ofclaim 1 wherein detecting the plurality of cardiogenic impedance signalsincludes detecting individual cardiac impedance signals by: measuring araw impedance signal along a selected sensing vector passing through theheart of the patient; and extracting a cardiogenic impedance signal (CI)from the raw impedance signal, wherein the cardiogenic impedance (CI)signal is representative of variations in impedance due to the beatingof the heart of the patient.
 3. The method of claim 1 whereinsignificant differences in the peak velocity delay times arerepresentative of significant mechanical dyssynchronies within theheart.
 4. The method of claim 1 wherein detecting abnormally contractingsegments includes detecting one or more of akinetic segments,hypokinetic segments and late contracting segments.
 5. The method ofclaim 1 wherein controlling at least one device function based on themeasure of mechanical dyssynchrony includes one or more of: recordingdiagnostic information, generating warning signals, and controllingdelivery of therapy.
 6. The method of claim 1 wherein the steps are allperformed by the implantable medical device.
 7. The method of claim 1wherein some of the steps are performed by the implantable medicaldevice and others are performed by an external system.
 8. A method foruse with an implantable medical device for implant within a patient, themethod comprising: detecting a plurality of cardiogenic impedancesignals along different sensing vectors within the patient; detecting ameasure of mechanical dyssynchrony in the heart of the patient based ona comparison of the cardiogenic impedance signals, including detectingabnormally contracting segments, if any, within the heart of thepatient; and controlling at least one device function based on themeasure of mechanical dyssynchrony; wherein detecting the measure ofmechanical dyssynchrony includes detecting differences in peak velocitydelay times observed within the cardiogenic impedance signals andidentifying late contracting segments within the heart of the patient byidentifying particular cardiogenic impedance signals wherein the peakvelocity delay time is significantly longer than the peak velocity delaytimes of the other cardiogenic impedance signals.
 9. A method for usewith an implantable medical device for implant within a patient, themethod comprising: detecting a plurality of cardiogenic impedancesignals along different sensing vectors within the patient; detecting ameasure of mechanical dyssynchrony in the heart of the patient based ona comparison of the cardiogenic impedance signals, including detectingabnormally contracting segments, if any, within the heart of thepatient; and controlling at least one device function based on themeasure of mechanical dyssynchrony; wherein detecting the measure ofmechanical dyssynchrony includes detecting differences in integralsderived from the cardiogenic impedance signals.
 10. The method of claim9 wherein detecting differences in the cardiogenic impedance signalintegrals includes: delivering a pacing pulse to the heart of thepatient; for each of the cardiogenic impedance signals, integrated aportion of the signal detected after pulse delivery; and comparing theintegrals derived from the cardiogenic impedance signals to generate themeasure of mechanical dyssynchrony.
 11. The method of claim 9 whereinsignificant differences in the cardiogenic impedance signal integralsare representative of significant mechanical dyssynchronies within theheart.
 12. The method of claim 9 further including identifyinghypokinetic segments within the heart of the patient by identifyingcardiogenic impedance signals with integrals significantly smaller thanthe integrals of the other cardiogenic impedance signals.
 13. The methodof claim 9 further including identifying akinetic segments within theheart of the patient by identifying cardiogenic impedance signals withintegrals below a minimum acceptable integral threshold.
 14. The methodof claim 9 wherein detecting the plurality of cardiogenic impedancesignals includes detecting individual cardiac impedance signals by:measuring a raw impedance signal along a selected sensing vector passingthrough the heart of the patient; and extracting a cardiogenic impedancesignal (Cl) from the raw impedance signal, wherein the cardiogenicimpedance (Cl) signal is representative of variations in impedance dueto the beating of the heart of the patient.
 15. The method of claim 9wherein detecting abnormally contracting segments includes detecting oneor more of akinetic segments, hypokinetic segments and late contractingsegments.
 16. The method of claim 9 wherein controlling at least onedevice function based on the measure of mechanical dyssynchrony includesone or more of: recording diagnostic information, generating warningsignals, and controlling delivery of therapy.
 17. The method of claim 9wherein the steps are all performed by the implantable medical device.18. The method of claim 9 wherein some of the steps are performed by theimplantable medical device and others are performed by an externalsystem.
 19. A system for use with an implantable medical device forimplant within a patient, the system comprising: a multiple cardiogenicimpedance signal detector operative to detect a plurality of cardiogenicimpedance signals along different sensing vectors within the patient;and a mechanical dyssynchrony evaluation system operative to detect ameasure of mechanical dyssynchrony in the heart of the patient based ona comparison of the cardiogenic impedance signals, including detectingabnormally contracting segments, if any, within the heart of thepatient; wherein to detect the measure of mechanical dyssynchrony themechanical dyssynchrony evaluation system is operative to deliver apacing pulse to the heart of the patient; for each of the cardiogenicimpedance signals, examine the signal to detect a maximum in a firsttime derivative of the signal after pulse delivery and then measure thetime delay from the pulse to the maximum in the first time derivative;and compare the peak velocity delay times derived from the cardiogenicimpedance signals to generate the measure of mechanical dyssynchrony.20. The system of claim 19 further comprising: a controller operative tocontrol at least one device function based on the measure of mechanicaldyssynchrony.
 21. The system of claim 20 wherein the controller includesa mechanical dyssynchrony-based cardiac resynchronization therapy (CRT)controller operative to control CRT based, at least in part, on themeasure of mechanical dyssynchrony.
 22. The system of claim 20 whereinthe controller includes a mechanical dyssynchrony-based warningcontroller operative to control the generation of warning signals inresponse to an increase in mechanical dyssynchrony.
 23. A method for usewith an implantable medical device for implant within a patient, themethod comprising: detecting a plurality of cardiogenic impedancesignals along different sensing vectors within the patient; detecting ameasure of mechanical dyssynchrony in the heart of the patient based ona comparison of the cardiogenic impedance signals, including detectingdifferences in integrals of the cardiogenic impedance signals; andcontrolling at least one device function based on the measure ofmechanical dyssynchrony.
 24. A system for use with an implantablemedical device for implant within a patient, the system comprising: amultiple cardiogenic impedance signal detector operative to detect aplurality of cardiogenic impedance signals along different sensingvectors within the patient; and a mechanical dyssynchrony evaluationsystem operative to detect a measure of mechanical dyssynchrony in theheart of the patient based on a comparison of the cardiogenic impedancesignals, including detecting abnormally contracting segments, if any,within the heart of the patient; wherein to detect the measure ofmechanical dyssynchrony the mechanical dyssynchrony evaluation system isoperative to detect differences in integrals derived from thecardiogenic impedance signals.
 25. The system of claim 24 furthercomprising: a controller operative to control at least one devicefunction based on the measure of mechanical dyssynchrony.
 26. The systemof claim 25 wherein the controller includes a mechanicaldyssynchrony-based cardiac resynchronization therapy (CRT) controlleroperative to control CRT based, at least in part, on the measure ofmechanical dyssynchrony.
 27. The system of claim 25 wherein thecontroller includes a mechanical dyssynchrony-based warning controlleroperative to control the generation of warning signals in response to anincrease in mechanical dyssynchrony.